The major objective of this research proposal is to study radiation-induced thyroid cancer by coordinated clinical and laboratory investigations. The clinical studies are designed to determine the continuing incidence of radiation-induced thyroid cancer and to evaluate methods of diagnosis and medical and surgical approaches to treatment. This will be accomplished by continuing the longitudinal study of patients who received childhood head and neck irradiation for benign conditions at Michael Reese Hospital. Of the 5,300 patients who were so treated, 2,000 have been examined in our program and another 1,400 have been evaluated elsewhere. In this population there is a 36% cumulative prevalence of thyroid nodules and among those who have had surgery, 36% have had thyroid cancer. The follow- up of this population will continue with the following aims: (1) to determine if radiation-induced thyroid cancer is continuing to occur and, if so, to provide an estimate of its incidence, (2) since the patients in this population are growing older, to determine if their radiation-induced thyroid cancers have the same age-dependent worsening prognosis as seen in the general population, and (3) to evaluate the treatment methods that have been used. Together these will provide the information to develop guidelines for the care of persons with a history of radiation. Our parallel studies will continue on other radiation-induced tumors which have been found, including those of salivary, neural, and parathyroid origin. Specific organ doses, as opposed to treatment doses, will be determined to obtain more precise dose-response curves and risk assessments. Studies to determine whether there are susceptibility factors for developing radiation-related neoplasms, especially familial ones, will be extended. Laboratory studies will focus on the role of serum thyroglobulin in the diagnosis of thyroid tumors. A subgroup of patients whose clinical evaluations, including thyroid scans, were normal, bur who had elevated serum thyroglobulin levels has been identified. In continuing the follow- up of these patients and a control group of patients we will determine the significance of the abnormal determination as a risk factor. This follow- up will also provide an opportunity to compare scans with ultrasound examinations of the thyroid. Factors contributing to the heterogeneity of the thyroglobulin molecule, with relation to thyroid neoplasms, will be studied.